Phosphate functionalization and enzymatic calcium mineralization synergistically enhance oligo[poly(ethylene glycol) fumarate] hydrogel osteoconductivity for bone tissue engineering

J Biomed Mater Res A. 2020 Mar;108(3):515-527. doi: 10.1002/jbm.a.36832. Epub 2019 Nov 26.

Abstract

A current approach in bone tissue engineering is the implantation of polymeric scaffolds that promote osteoblast attachment and growth as well as biomineralization. One promising polymer is oligo[poly(ethylene glycol) fumarate] (OPF), a polyethylene glycol-based material that is biocompatible, injectable, and biodegradable, but in its native form does not support robust bone cell attachment or growth. To address this issue, this study evaluated the osteoconductivity of bis[02-(methacryloyloxy)ethyl] phosphate (BP) functionalized OPF hydrogels (OPF-BP) using MC3T3-E1 pre-osteoblast cells, both before and after enzymatic mineralization with a calcium solution. The inclusion of negatively charged functional groups allowed for the tailored uptake and release of calcium, while also altering the mechanical properties and surface topography of the hydrogel surface. In cell culture, OPF-BP hydrogels with 20 and 30% (w/w) BP optimized osteoblast attachment, proliferation, and differentiation after a 21-day in vitro period. In addition, the OPF-BP30 treatment, when mineralized with calcium, exhibited a 128% increase in osteocalcin expression when compared with the non-mineralized treatment. These findings suggest that phosphate functionalization and enzymatic calcium mineralization can act synergistically to enhance the osteoconductivity of OPF hydrogels, making this processed material an attractive candidate for bone tissue engineering applications.

Keywords: bis[2-(methacryloyloxy)ethyl] phosphate (BP); bone tissue engineering; osteoblast; osteoconduction; phosphate functional groups.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Regeneration / drug effects*
  • Bone and Bones / cytology
  • Bone and Bones / drug effects
  • Calcium / metabolism*
  • Cell Line
  • Fumarates / chemistry
  • Fumarates / pharmacology*
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Methacrylates / chemistry
  • Methacrylates / pharmacology*
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology*
  • Tissue Engineering

Substances

  • 2-(methacryloyloxy)ethyl phosphate
  • Fumarates
  • Hydrogels
  • Methacrylates
  • poly(ethylene glycol fumarate)
  • Polyethylene Glycols
  • Calcium